POS0888 NON-SURGICAL LOCAL TREATMENTS FOR DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW
Authors: C. Campochiaro, Y. A. Suliman, M. Hughes, J. Schoones, D. Giuggioli, P. Moinzadeh, N. Maltez, L. Ross, M. Baron, L. Chung, Y. Allanore, C. P. Denton, O. Distler, T. Frech, D. Furst, D. Khanna, T. Krieg, M. Kuwana, M. Matucci-Cerinic, J. Pope, A. Alunno
Journal: Annals of the Rheumatic Diseases (2022)

Background Digital ulcers(DUs) in systemic sclerosis(SSc) represent a major clinical challenge. There are no recommendations for the local management of SSc-DUs. Systemic therapy is considered the standard of care. However, there is a strong rationale for local approaches to DU by avoiding side effects from systemic therapies. The World Scleroderma Foundation DU Working Group intends to develop evidence-based recommendations for DU management including local, non-surgical treatment(ln-sT). Objectives To summarise the literature on the safety and efficacy of ln-sT for SSc-DUs. Methods A systematic literature review(SLR) of papers describing the use of ln-sT for DU in SSc was performed up to May 2021 according to the PICO framework. References were independently screened by two reviewers who independently assessed the full text of eligible articles and extracted data. Results Among 790 retrieved references, 12 were included. Median(range) number of patients per study was 9(7–84), mean age ranging from 37 to 62.5 years. In 5(41%) studies a control group was included. Background systemic therapies are summarized in Table 1. The most studied treatment was botulin toxin A(BTA). It was used as hand injection in 3 studies (median dose ranging from 90 to 150 U) and as 50 U single finger injection in 1 study. Healing rate after a median time of 8-49 weeks ranged from 71% to 100%. In 2 studies a reduction in VAS pain was observed from 20% to 100%. Transient muscle weakness was the most common side effect in 10% of patients. Amniotic(Am) and hydrocolloid membranes(HyM) were used in 1 study each. They were associated with a good healing rate, statistically significant for the HyM. Tadalafil 2% cream was studied in 1 study and was associated with a reduction in the median DU number from 1.6 to 1 per patient after a median time of 4 weeks and a reduction by 1.4 point in the 10-mm VAS scale. Vitamin E gel was shown to be associated with a statistically significant reduction in the healing time compared to SoC alone in 1 RCT(13.2 ± 2.7 versus 20.9 ± 3.6 weeks, P=&lt;0.001). Low-level light therapy, hydrodissection and corticosteroid injection and extracorporeal shock wave(ESW) were evaluated in 1 study each. They were all associated with positive outcomes which was statistically significant only for the ESW. The only negative trial examined dimethyl sulfoxide and was associated with local toxicity. Table 1. Characteristics of the studies. Treatment Type of study Patients Baseline DU Background therapy (% ) ETA CCB APA PG ARB ACE-I PDE-5i IS Follow-up (weeks ) Healing rate(%)* Pain Reduction (VAS/10 ) Comparator Hydrodissection and corticosteroid injection P 12 0 2 33 4.4 Rheumatoid Arthritis Tadalafil 2% Vitamin E gel RRCT 1513 1.6(1)3.5±2.3 0 46 27 00 13 0 7 0 4 24 1(1)Reduced time to heal** 1.4 SoC AmHyM RP 67 310 00 10028 0 00 0 28 170 3314 38 10090** SoC BTA Median 90 U per handHigh-concentration hand100 U non-dominant handSingle finger 50 U RRPP 772010 3145 71140 71855 855100 851420100 1414 71 8 49812 777175100 20%100% Untreated CH Low-level light therapy P 8 10 25 37 0 25 37 8 100 ESW P 9 49 33 55 66 11 44 4 41** 1.31 Dimethyl sulfoxide DBRCT 84 No change, skin toxicity with 70% formulation *Unless otherwise stated. **Statistically significant. ARB= angiotensin receptor antagonist. ACEi= ACE inhibitors. APA= anti-platelet agents. CCB= calcium channel blockers. CH= contralateral hand. DBRCT= double blind randomized-controlled trial. ETA = endothelin antagonist. IS= immunosuppression. PG= prostaglandins. PDE-5i= Phosphodiesterase type-5 inhibitors. P = prospective. R = retrospective. SoC= standard of care (as per local protocol). Conclusion Our SLR supports interest to develop ln-sTs for SSc-DUs. The number of studies is limited and mainly case reports and small single studies are present. Treatments were well tolerated and there was evidence of efficacy for BTA, vitamin E, ESW and HyM in refractory DUs. The evidence is not robust and confounding factors (vasodilators background therapies) could impact on the findings. Future research is indicated to conduct larger, well-designed studies. Disclosure of Interests Corrado Campochiaro: None declared, Yossra A. Suliman: None declared, Michael Hughes Speakers bureau: Actelion pharmaceuticals, Eli Lilly, and Pfizer, outside of the submitted work., Jan Schoones: None declared, Dilia Giuggioli: None declared, Pia Moinzadeh Speakers bureau: speaking fees from Actelion pharmaceuticals and Boehringer Ingelheim, Nancy Maltez: None declared, Laura Ross: None declared, Murray Baron: None declared, Lorinda Chung: None declared, Yannick Allanore: None declared, Christopher P Denton: None declared, Oliver Distler Speakers bureau: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Tracy Frech: None declared, Daniel Furst: None declared, Dinesh Khanna Speakers bureau: Janssen and Eicos Sciences, Inc., Thomas Krieg: None declared, Masataka Kuwana Speakers bureau: Speakers fees from AbbVie, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai, Eisai, GlaxoSmithKline, Janssen, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi, and Consultant fees from AstraZeneca, Boehringer Ingelheim, Corbus, Kissei, Mochida, outside of the submitted work., Marco Matucci-Cerinic: None declared, Janet Pope: None declared, Alessia Alunno: None declared